Toxic Substances, pesticides and others

The report's recommendations, which applied to testing conducted for pesticide as well as other chemical exposures from toxic substances to air contaminants, did not call for an outright ban on human testing, which was urged by many environmental groups. But it said intentional dosing of volunteers should only be considered by the agency if it addresses regulatory questions that cannot be answered with animal studies or other testing that does not involve humans, and that the benefits of such research "must outweigh" risks to test subjects who are exposed.

The recommendations are expected to get close attention from EPA, which is drafting a proposed rule or policy on testing involving the intentional dosing of humans, which typically involves volunteers who are compensated for their efforts. The agency has struggled with the issue since the late 1990s when the pesticide industry began submitting data from clinical trials to assert lesser effects from pesticides. Those efforts were aimed at countering tougher pesticide exposure standards set by Congress in the Food Quality and Protection Act of 1996.

The academies report also urged EPA to add several procedures to ensure that such studies adhere to the more rigorous ethical and scientific requirements. Researchers conducting such studies should take additional steps, including the equitable selection and recruitment of human subjects and obtaining informed consent from those volunteers. EPA should place added scrutiny on any study nvolving intentional dosing of humans by requiring that such research first be reviewed through an Institutional Review Board, or an equivalent panel in other countries.

To supplement that layer of oversight, the committee also recommended that EPA create a Human Studies Review Board to evaluate all human dosing studies that could be used to make regulatory decisions, when that research is either sponsored or carried out by the agency. Pesticide companies and other private entities would be urged to voluntarily submit their plans to the review board prior to launching a study, the panel said.

Green Light for More Testing?

Environmental groups derided the academies panel report Feb. 19, arguing that more stringent requirements could not address a knot of ethical considerations that would remain if any human testing is considered by the agency.

"If the EPA begins to accept human experiments we expect to see companies taking advantage of any and all ambiguities in the guidelines and to continue performing unethical tests that will help keep unsafe chemicals in our food and water," according to Richard Wiles, senior vice president for the Environmental Working Group.

The EWG issued a report in 1998 alleging various abuses in past human testing supported by the pesticide industry, including paying volunteers as much as $1,000 each to participate and misrepresenting the tests as part of drug research.

EPA attempted to institute a ban in a December 2001 press release that pledged to refrain from using such tests for regulatory decisions until the academies study was completed, but the policy was challenged by the pesticide industry and struck down in June 2003 federal court decision.

The agency published an advance notice of proposed rulemaking in May 2003 asking what standards should be applied to third-party human studies and could publish a formal proposal by year's end(68 Fed. Reg. 24,410; 88 DEN A-18, 5/7/03).

The pesticide industry largely applauded the academies report findings, saying past research has been conducted in accordance with many of the stringent guidelines referred to in the report, including the Common Rule, a set of federal regulations governing the protection of human subjects. The regulations were simultaneously adopted by 15 agencies and departments in 1991, including EPA and the departments of agriculture, defense, energy, and health and human services.

The academies report recommended EPA adopt additional provisions of the Common Rule, Subpart D, which are designed to provided more stringent protections for children in any intentional dosing studies.

Children as Potential Test Subjects

Members of the academies committee that oversaw the report acknowledged that it falls short of calling for a ban on any form of human testing, including pesticide other chemical testing of children or other vulnerable populations, such as pregnant women. In part, that is because it is hard to envision research on those populations that would be considered "of enormous public importance" and meet the tough ethical and scientific hurdles recommended in the report, according to Ellen Wright Clayton, a member of the academies panel and professor of pediatrics with Vanderbilt University.

Clayton said that while it may be "possible to imagine a study that might meet" such criteria, "the committee decided not speculate on what ethical study could be conducted" using child test subjects.

Michael Taylor, a panel member and director of risk, resources, and environmental management for Resources for the Future, said EPA has in the past sponsored some research using children as test subjects to measure the effects of various pollutants. He noted that the academies' recommendations were aimed at the broad array of testing conducted for and by EPA and not limited to pesticides or other chemicals.

Thomas Louis, a panel member and professor with Johns Hopkins University's Bloomberg School of Public Health, said that while the committee did not "close the door" to child exposure studies, he could not think of a pesticide or other chemical study that would provide the high degree of benefits to society and meet the tougher ethical and scientific criteria recommended in the report.

The academies report, Intentional Human Dosing Studies for EPA Regulatory Purposes, Scientific and Ethical Issues, is available at http://www.nap.edu on the World Wide Web.